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Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans

NCT00246714 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 16

Last updated 2008-04-15

No results posted yet for this study

Summary

A number of diseases lead to a so called systemic inflammatory response syndrome (SIRS). This excessive response is self-destructive and leads to major complications of the initial disease: dysfunction of the microcirculation, systemic vasodilation, and increased capillary leakage and oedema. Animal studies have shown that pre-treatment with endotoxin (lipopolysaccharide or LPS) suppress the excessive immune response and when rechallenged, the animal survive a normally lethal dose of endotoxin.

Besides a diminished cytokine response, an increased production of leucocytes in the bone marrow and an increased phagocytosis after pre-treatment with endotoxin is seen. The combination of these factors: diminished systemic inflammatory response and increased cellular immunity makes that endotoxin tolerance is a useful tool for preventing the complications after an excessive inflammatory response.

Further, the presence of cross-tolerance has also been shown: Endotoxin tolerant mice survive more after induction of a normally lethal fungal infection. Endotoxin tolerance is also protective for ischemia/reperfusion injury in kidneys, heart and liver. Little data is known about endotoxin tolerance in human.

The purpose of this study is to induce a state of tolerance through 2 different administration schedules and monitor the effect of tolerance on pro- and anti-inflammatory cytokines, other inflammatory parameters and different proteins involved in the signalling pathway. The effects of tolerance on vascular reactivity will be determined. Finally, the effect of tolerance on ischemia-reperfusion injury will be investigated.

Conditions

  • Endotoxemia

Interventions

DRUG

repeated injections of endotoxin during 5 days

Sponsors & Collaborators

  • Radboud University Medical Center

    lead OTHER

Principal Investigators

  • Peter Pickkers, MD PhD · Radboud University Nijmegen Medical Center

Study Design

Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
35 Years
Sex
MALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2005-10-31
Primary Completion
2007-12-31
Completion
2007-12-31

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00246714 on ClinicalTrials.gov